A major hurdle in developing tissue engineered products and therapies is the lack of suitable substrates which can act as cell delivery platforms and form three dimensional scaffolds for cells to grow and to provide the mechanical support during the tissue regeneration process. Such polymer systems could be useful in arthroscopic delivery of cells to repair damaged tissues in the body. These cell delivery systems allow the exploitation of the full potential of tissue engineering field and assist the body to repair its damaged tissues and organs. Despite many recent advances in the design and development of suitable polymers for fabricating scaffolds, the existing polymer systems do not meet the demanding criteria for cell delivery.
Several criteria must be achieved if such a polymer system is to be useful for cell delivery. It must be non cytotoxic before and after curing and provoke no inflammatory response in the body. The method of the initiation of polymerisation to form the polymer network should be tolerant to the cells and other components used. The polymer network formed should have sufficient porosity to facilitate cell-polymer interactions, and to allow the transport of nutrients to the cells, and also provide sufficient space for the growth of the extra cellular matrix. A polymer system that can be tailored to have different mechanical properties depending on the type of tissues to be regenerated will have advantages in regenerating different types of biological tissues. For example, a system that sets to a high modulus material would be useful in orthopaedic applications. Furthermore, the viscosity of the polymer/cell mixture should be such that it can be delivered using a syringe or an arthroscopic method. This provides substantial advantages in employing minimally invasive surgical techniques to be used in treatments to repair damaged body tissues such as fractured bones, damaged knee cartilages, or other body tissues and organs.
Natural polymers such as alginate, fibrin, argrose, collagen, methylcellulose, hyluronon and peptide-based hydrogels have been investigated as cell delivery systems with some success. Primarily due to the ability of such polymers to accommodate large quantities of water and their good biocompatibility, cells stay viable in those systems. Accordingly, formulations based on natural polymers have been developed primarily as cell encapsulation products. The formation of a gel from these polymers is achieved by exploring the thermo reversible characteristics of some of the polymers or the use of ionic strength to transform to a gel in some cases. These properties of natural and some synthetic polymers have been explored as cell encapsulation systems.
Chemical modification to introduce cross linkable functional groups has also been investigated. A major draw back of such polymer systems is the very poor mechanical strengths of the cross linked hydrogel. While these systems are useful as cell-encapsulation systems, their utility in tissue engineered products and therapies are limited, particularly when high mechanical strength of the gel is required.
Likewise, synthetic polymers have been investigated for preparing hydrogels for cell encapsulation/delivery purposes. Hydrophilic polymers such as poly(ethylene) glycol, end functionalized with acrylates have been investigated for cell encapsulation. The gels formed by cross linking are generally mechanically very weak, not too different to those based on natural polymers. Although synthetic polymers may provide the best option to develop systems with appropriate mechanical strength, synthetic polymer systems reported to date do not provide adequate mechanical properties nor do they have the ability to incorporate cells without affecting their viability.
Repair and regeneration of load-bearing tissues such as cartilage and bone require the cell delivery polymer system to have sufficient mechanical strength over a considerable period of time for the tissue regeneration to be complete. Ideally the mechanical strength should be comparable to that of the type of tissue to be repaired or regenerated. A mechanically inferior gel would most likely disintegrate due to compressive, torsional or tensile forces such tissues are subjected to well before the defect site is repaired. The gels based on natural polymers and synthetic polymers in general do not provide sufficient mechanical support in such situations. Accordingly, there is a need for cell delivery polymer systems which can be tailored to have sufficient mechanical strength depending of the type of tissue to be repaired/regenerated. It is also a requirement that the gels maintain cell friendly environment before and after cross linking the polymer. Ideally, the polymer should degrade and the degradation products be completely released from the body once the damage is repaired.